Abstract in English:Cuba’s nascent biotechnology sector began making scientific breakthroughs in the 1980s, including the isolation of human leukocyte interferon alpha (1981) and the development of the world’s first safe, effective meningitis BC vaccine (1989). With positive results in hand and a growing R&D pipeline, the island nation established a national regula-tory authority (NRA) to implement and oversee best practices for all pharmaceuticals and medical devices, domestically produced and imported, used in the country’s universal health system. Founded in 1989, Cuba’s Center for State Control of Medicines and Medical Devices (CECMED) is the entity charged with regulating all phases of scientific innovation for health, from clinical trial design to postmarketing surveillance. Dr Rafael Pérez Cristiá, Distinguished Member of the Cuban Academy of Sciences, has been Director General of CECMED since 2000, overseeing regulation and control of unique and innovative biotechnology products and the concomitant evolution of the nation’s regulatory authority. Under his guidance, CECMED has regulated unique therapies, vaccines, and pharmaceutical products—some unavailable anywhere else in the world—aimed at improving population health both at home and abroad. Recognized internationally as one of the top 20 countries with a safe and reliable biotechnology industry and regulatory authority, Cuba is having a measurable impact on public health. In this exclusive interview, Dr Pérez Cristiá, explains how a small, resource-scarce country has rocketed into the global biotech elite—and how it intends to stay there.
Abstract in English:SUMMARY INTRODUCTION Interferons have been used to treat basal cell carcinoma with positive results. Cuba’s Genetic Engineering and Biotechnology Center developed HeberPAG, a combined formulation of interferons alpha-2b and gamma, for treatment of basal cell carcinoma of any size, subtype and location. OBJECTIVE Evaluate the safety and effectiveness of using Heber-PAG in primary care to treat basal cell carcinomas. METHODS A descriptive observational study was conducted of basal cell carcinoma treated with HeberPAG. The sample comprised 21 tumors in 19 patients who met selection criteria. The dose was 3.5 million international units of antiviral activity administered by perilesional infiltration 3 times a week for 3 weeks. Clinical monitoring and laboratory testing of patients was conducted before treatment initiation and at 4, 8, 16 and 52 weeks. Variables recorded were: age, sex, skin phototype, clinical and histologic type, clinical response to treatment, changes in tumor diameters and adverse events. Four response categories were included: complete response, partial response, stable disease and progressive disease. Data were recorded in medical dossiers. Microsoft Excel and SAS were used for data management and calculation of measures of frequency, central tendency and dispersion. RESULTS Of 19 patients studied, 63% were male, and 63% aged 61–80 years. At 16 weeks, there was an objective response in 76% of tumors (8 complete and 8 partial responses). Fewer objective responses were seen in rodent ulcer, advanced invasive and sclerosing clinical types and in the sclerodermiform histologic type. Mean sum of diameters decreased from 36.9 mm (SD 4.1 mm) to 10.3 mm (SD 18.3 mm). One-year recurrence was 10%. The most common adverse reaction was flu-like syndrome, consisting of fever, malaise, joint pain and muscle pain. CONCLUSIONS Basal cell carcinoma can be successfully treated in primary care settings with a combination of interferons alpha-2b and gamma administered by trained personnel. At the dose employed in this study, the formulation produces a favorable response in basal cell carcinomas of low clinical and histologic risk, and is well tolerated, with only mild side effects. CONTRIBUTION OF THIS RESEARCH This study demonstrates the feasiblity of treating basal cell carcinoma in primary care settings with a combined formulation of interferons alpha-2b and gamma, enabling management in primary care of a cancer usually treated in hospital.
Abstract in English:ABSTRACT INTRODUCTION Cancer is a major public health problem worldwide and in Cuba. Approximately one third of cancer patients develop a brain metastasis. Despite this, epidemiological studies are scarce, internationally and in Cuba; published research is mainly limited to autopsy studies and hospital case series. OBJECTIVE Characterize patients with brain metastases residing in Habana del Este Municipality, Havana, Cuba, with respect to demographics, metastasis location and primary tumor site. METHODS A retrospective descriptive study was carried out with data for all patients with histologically confirmed cancer diagnosed in 2014 and registered in primary health care in Habana del Este Municipality. Diagnostic reports from computed tomography and/or magnetic resonance imaging were used to identify patients with brain metastases. Study variables were age, sex, skin color, number and location of brain metastases, control of primary tumor, and presence of extracranial metastases. Percentages were calculated and presented in tables. RESULTS We identified 832 cancer patients in the Habana del Este population of 181,473 (prevalence 458.5 per 100,000 population). Among patients with cancer, 27.6% (230/832) had brain tumors, among which 83% (191/230) were brain metastases and 17% (39/230) primary tumors, a ratio of 4.9:1. Brain metastases appeared in 23% (191/832) of cancer patients (prevalence 105.2 per 100,000 population). Among patients with brain metastases, 48.2% (92/191) were aged 41–60 years and 61.3% (117/191) were female sex. The majority, 59.7% (114/191) had multiple metastases. The most frequent primary tumor location was the breast (40.8%, 78/191), followed by the lung (31.9%; 61/191); 46.8% (211/451) of brain metastases were in the parietal lobe. CONCLUSIONS Brain metastases are more prevalent in this Cuban municipality than reported in other countries, but they constitute a higher proportion of cancer cases than seen in other population-based studies. The study’s results underline the importance of detecting brain metastasis early, to permit timely interventions to improve quality of life and survival. CONTRIBUTION OF THIS RESEARCH This is the first epidemiological study of brain metastases in Cuba and one of the few carried out internationally.
Abstract in English:ABSTRACT INTRODUCTION Reference values for liver stiffness for healthy individuals vary worldwide. Different optimal cutoff values correspond to the stages of fibrosis in chronic liver disease. OBJECTIVES Characterize the distribution of liver stiffness in Cuban adults without liver disease and its association with age, serum uric acid and body mass index. METHODS A cross-sectional study was performed of 110 plasma donors recruited from the Havana Province Blood Bank January 2016 through February 2017. Measurements of liver stiffness were performed using a FibroScan elastography device on the same day of laboratory analyses and abdominal ultrasound. The Pearson coefficient was used to assess correlations, and the reference range was calculated using the mean and its 95% confidence interval. RESULTS Liver stiffness values observed ranged from 2.2–6.3 kPa. The reference range (95% CI) for the 110 subjects without known liver disease was 4.2–4.6 kPa (mean 4.4). A positive correlation was observed between liver stiffness measurements and body mass index (r = 0.255, p <0.01) and serum uric acid (r = 0.266, p <0.01). There was no correlation between liver stiffness and age. Liver stiffness in women was similar to that of men, 4.3 (2.4–6.1) and 4.5 (2.2–6.3) kPa, respectively (p = 0.086). CONCLUSIONS Liver stiffness in Cuban adults without liver disease ranges from 2.2–6.3 kPa. The reference range is 4.2–4.6 kPa. Body mass index and serum uric acid levels are positively associated with liver stiffness. CONTRIBUTION OF THIS RESEARCH This is the first Cuban study using FibroScan to measure liver stiffness; its results will enable better assessment of liver disease in clinical practice.
Abstract in English:SUMMARY INTRODUCTION IgA deficiency is a primary immunodeficiency predominantly due to an antibody defect, for which there is no replacement therapy. Treatment consists of prevention and treatment of infections and other associated conditions. Given the immunomodulatory and regulatory properties of the redox balance of ozone therapy in infectious and inflammatory conditions, evaluation of its effect on IgA deficiency is of interest. OBJECTIVE Assess the benefits and possible adverse effects of ozone treatment in patients with IgA deficiency. METHODS A monocentric randomized controlled phase 2 clinical trial (RPCEC 00000236) was carried out, after approval by the Institutional Ethics Committee of the Roberto Rodríguez Fernández Provincial General Teaching Hospital in Morón, Ciego de Ávila Province, Cuba. Included were 40 patients aged 5–50 years, distributed in 2 groups of 20, after agreeing to participate and signing informed consent. The experimental group received 2 cycles of ozone by rectal insufflation for 20 days (5 times a week for 4 weeks each cycle) with a 3-month interval between cycles, for a total of 40 doses, with age-adjusted dose ranges. The control group was treated with leukocyte transfer factor (Hebertrans), 1 U per m2 of body surface area subcutaneously, once weekly for 12 weeks. Frequency of appearance and severity of clinical symptoms and signs of associated diseases, serum immunoglobulin concentrations and balance of pro-oxidant and antioxidant biomarkers were recorded at treatment initiation and one month after treatment completion. Therapeutic response was defined as complete, partial, stable disease or progressive disease. Descriptive statistics and significance were calculated to compare groups and assess effect size. RESULTS One month after treatment completion, 70% of patients in the experimental group experienced significant increases in IgG (p = 0.000) and IgM (p = 0.033). The experimental group also displayed decreased pro-oxidation biomarkers, glutathione modulation and increased antioxidant enzymes, with reduced oxidative stress; none of these occurred in the control group. Complete therapeutic response was achieved in 85% of patients in the experimental group and only 45% in the control group. Mild, transient adverse events were reported in both groups. CONCLUSIONS Ozone therapy by rectal insufflation is a suitable therapeutic option for treating IgA deficiency because it produces antioxidant and immunomodulatory effects and is feasible, safe and minimally invasive. CONTRIBUTION OF THIS RESEARCH This paper introduces in Cuba a new treatment a for IgA deficiency, with immunomodulatory and antioxidant effects offering substantial clinical benefits to patients with this immunodeficiency.
Abstract in English:SUMMARY INTRODUCTION Recent decades have seen an uptick in suicide attempts and completed suicides among adolescents and young adults worldwide. In the Americas, including Cuba, suicide is the third leading cause of death in adolescents (ages 10–19 years). OBJECTIVE Characterize the epidemiology of attempted and completed suicide in Cuban adolescents from 2011 through 2014. METHODS A descriptive epidemiological study was carried out. The information was gathered from morbidity records for suicide attempts and mortality records for suicide deaths in adolescents, taken from the Cuban Ministry of Public Health’s Medical Records and Health Statistics Division database for January 1, 2011 through December 31, 2014. Variables were sex, age, occupation or employment status, and suicide method. Suicide attempt incidence rates and suicide mortality rates by age group per 100,000 population (crude, adjusted and age/sex specific), mortality sex ratio and attempt/suicide ratio were calculated. Relative change was calculated as a percentage, as were frequencies by variable for attempted suicide and suicide, and by age and sex for method used. RESULTS A total of 19,541 suicide attempts and 149 suicides were reported. Average annual numbers were 4,885.2 suicide attempts and 37.2 suicides (131:1 ratio). There were 3,966 suicide attempts among boys, for a sex ratio of 0.25:1. Age-adjusted suicide attempt rates decreased from 391.8 per 100,000 population to 304.5 (22.3% reduction over the study period). Boys accounted for 107 of 149 suicide deaths, for a sex ratio of 2.5:1. Age-adjusted suicide mortality rates decreased from 2.8 to 2.3 per 100,000 population (17.9% reduction). The group aged 15–19 years had the highest age-adjusted suicide rate (3.9 per 100,000 population) and contributed the most deaths (114/149, 76.5%), although it did experience a 31.8% reduction over the study period. The group aged 10–14 years recorded a relative increase of 60% over the study period. Hanging was the most common suicide method (116/149, 77.9%). The suicide rate in Cuban adolescents (2.6 per 100,000 population, 3.7 in boys and 1.5 in girls) is less than that reported by the Region of the Americas between 2005 and 2009, 3.7 per 100,000 population (5/100,000 in boys and 2.3/100,000 in girls). CONCLUSIONS Suicide rates in Cuban adolescents are lower than reported elsewhere in the Americas. Suicide attempts and suicide rates decreased modestly between 2011 and 2014. Hanging is the most commonly used method. The highest rates occur in the group aged 15–19 years, but those aged 10–14 years showed a relative increase over the study period. These results update the epidemiology of suicide in Cuban adolescents and demonstrate the extent of the problem. Suicides and suicide attempts show opposite patterns in boys and girls; suicides are more frequent among boys while suicide attempts are more frequent among girls. CONTRIBUTION OF THIS RESEARCH These results update the epidemiology of suicide in Cuban adolescents and reveal the extent of the problem for one of the main preventable causes of death in this age group.
Abstract in English:Haiti is a country that appears fleetingly in the English-speaking media, when stricken by disaster or more recently by epithets. Perhaps few are aware that Haiti was the first independent nation in Latin America and the Caribbean, and the world’s first black republic—independence declared on January 1, 1804—in a revolution led by former slaves who defeated Napoleon’s 40,000-strong colonial forces. Or that, when others abandoned the independence wars against Spain, Simón Bolívar appealed to Haitian president Alexandre Pétion and with Pétión’s troops and material aid, went on to free slaves across Spanish-held colonies in Latin America. Over the centuries, the Haitian people have indeed been beset by disasters, both natural and man-made. But they have also stood against daunting odds and have received solidarity from their hemispheric neighbors, Cuba among the countries allied with Haiti’s attempts to provide for its people. In this Retrospective, MEDICC Review reprints excerpts from a blog by Senior Editor Conner Gorry, who, during February and March 2010, was embedded in the disaster-response medical team sent from Cuba after the January 12 earth-quake. The team reinforced nearly 500 Cuban health per-sonnel already on the ground long term in 120 communities. Some 700 of the 1300 new arrivals were students or graduates of Cuba’s Latin American School of Medicine from 27 countries. Haitian graduates now number 1044. The international contingent (named after Henry Reeve, a Brooklyn-born general in Cuba’s own independence struggle)—became the largest medical relief effort assembled after the quake. The vivid stories here take us back to the urgency and chaos of those first weeks and months after disaster struck. But Haitian, Cuban and other Cuban-trained doctors dedicated to Haiti’s recovery—its long-term health care needs and strengthened public health system—provide an example of commitment to social equity and human solidarity in the face of enormous challenges. And their work with those from other countries proves effective cross-border, cross-cultural collaboration can work. Today, there are 664 Cuban health professionals collabo-rating in Haiti, 175 of them doctors posted throughout the country. In 2017 alone, they carried out 2.64 million patient consults, performed 40,842 surgeries, and delivered 5788 babies (many times working with local midwives). They labor in 21 community reference hospitals built with funds from Venezuela; 31 rehabilitation centers, also built after the 2010 earthquake; 14 health centers; and 29 sentinel sites for epidemiological surveillance (mainly for cholera and vector-borne diseases). A national workshop for orthotics and prosthetics was also established to assist earthquake victims, with equipment and other resources provided by Cuba. The Editors